<p>It is estimated that 1 in 500 Americans are inflicted with
type I diabetes (T1D) with approximately 18,000 children and adolescents diagnosed
each year. Islet/β
cell replacement with long-lasting glucose-sensing and insulin-releasing
functions has the potential to eliminate the need for insulin injections and
minimize complications for individuals with T1D. However, limitations remain
precluding it from widespread clinical use, including i) limited donor supply,
ii) significant loss of functional islet mass upon transplantation, iv) limited
functional longevity, and v) need for life-long systemic immunosuppression. To restore glucose-responsive
insulin-release back to the patient’s body without the need for systemic
immunosuppression, our approach involves a subcutaneous injection using a novel
fibril-forming biologic, type I oligomeric collagen (Oligomer). Oligomer
protects and in situ encapsulates replacement cells beneath the skin by
transitioning from a liquid to a stable collagen-fibril scaffold, within seconds,
just like those found in the body’s tissues. Preclinical validation studies in
streptozotocin-induced diabetic mice show that replacement of islets at a dose
of 500 or 800, results in a rapid (within 24 hours)
reversal of hyperglycemia. All animals receiving syngeneic islets maintained
euglycemia for beyond 90 days, while >80% of animals receiving allogeneic or
xenogeneic (rat) islets remained euglycemia for at least 50 days.
Histopathological analysis of Oligomer-islet implants showed normal morphology
with no apparent evidence of a foreign body response and immune cell
infiltrate. To our knowledge, this is the first
report of an injectable subQ islet transplant strategy that yields rapid
lowering and extended glycemic control without systemic immunosuppression.</p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/9104906 |
| Date | 02 August 2019 |
| Creators | Clarissa L Hernandez Stephens (7041350) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Engineering_a_Pancreatic_Islet_Microenvironment_for_Improved_Survival_Function_Protection_and_Delivery/9104906 |
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